黴菌感染
Aspergillosis: Treatment of invasive aspergillosis in adults
Mucormycosis: Treatment of invasive mucormycosis in adults

Antifungal Agent, Azole Derivative
Isavuconazonium sulfate is a prodrug that is rapidly hydrolyzed in the blood to active isavuconazole. Isavuconazole inhibits the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is responsible for the conversion of lanosterol to ergosterol. An accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane weakens the membrane structure and function.

Distribution:
1. Vss: ~450 L
2. Protein binding: >99% (primarily to albumin)
Metabolism:
Isavuconazonium sulfate (prodrug) is rapidly hydrolyzed in the blood by esterases to active isavuconazole and an inactive cleavage product. Isavuconazole is metabolized by CYP3A4, CYP 3A5, and UGT
Excretion:
1. Urine (<1% as unchanged isavuconazole); feces (33% as unchanged isavuconazole)
2. Half-life elimination: 130 hours

1. Hypersensitivity to isavuconazonium sulfate (eg, isavuconazole) or any component of the formulation
2. Concurrent use of strong CYP3A4 inhibitors or inducers
3. Familial short QT syndrome

Use of alternative antifungals is recommended in pregnant women

The manufacturer recommended breastfeeding be discontinued during maternal isavuconazonium sulfate therapy

1. Cardiovascular: Peripheral edema
2. Central nervous system: Headache, fatigue, insomnia
3. Endocrine & metabolic: Hypokalemia
4. Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, constipation
5. Hepatic: Increased liver enzymes
6. Respiratory: Dyspnea, cough

1. Initial: 372 mg (isavuconazole 200 mg) every 8 hours for 6 doses
2. Maintenance: 372 mg (isavuconazole 200 mg) once daily; start maintenance dose 12 to 24 hours after the last loading dose
3. Duration: Minimum of 6 to 12 weeks, although duration is highly dependent on degree/duration of immunosuppression, disease site, and evidence of disease improvement

Not recommened

No dosage adjustment necessary.

1. Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary
2. Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling

Refrigerate between 2 and 8 degrees C